Aromatic amines are environmental carcinogens which are heavily used in industry and also occur in non-industrial environments such as tobacco smoke, polluted air, broiled meats, and hair dyes. An intriguing feature of aromatic amine carcinogenesis is that introduction of an orth-methyl group increases carcinogenecity. The objective of this proposal is to elucidate the metabolism and mechanism of action of the carcinogens 2-amino-3-methylnaphthalene and 3,2'dimethyl-4-aminobiphenyl. These chemicals cause colon cancer in male rats and mammary and colon cancer in female rats and are important model compounds for the study of these major cancers as well as being representative ortho-methyl aromatic amines. The activation and detoxification pathways of these compounds will be studied in vivo and in vitro using the 14C labelled compounds. Likely proximate and ultimate carcinogens, including those arising from oxidation of both the methyl and amino groups, will be synthesized and assayed for mutagencity and carcinogenicity. The effects of environmental modifiers on activation pathways and the interaction of the proximate form with cellular macromolecules in target tissues will also be studied. The results of these studies will increase our understanding of the mechanism of action of these and other carcinogenic aromatic amines.